Survivin 反义核酸联合紫杉醇对皮下荷瘤Balb/c 小鼠模型的治疗作用  

The therapeutic effects of survivin antisense nucleic acid combined with paclitaxel on subcutaneous xenograft mouse model of Balb/c

作　　者：吴丽贤[1] 黄立森 陈瑞家 田崛 柯方[2] 

机构地区：[1]福建医科大学药学院药理系,福建省天然药物药理学重点实验室,福建福州350108 [2]福建医科大学药学院药化系,福建福州350108

出　　处：《西安交通大学学报（医学版）》2015年第4期467-471,共5页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：国家自然科学基金资助项目(No.30901824,No.81273541);福建省自然科学基金杰出青年项目(No.2011J06013)~~

摘　　要：目的研究survivin反义核酸与紫杉醇联合应用对皮下荷瘤Bal b/c小鼠模型的治疗作用,并初步探讨对其抗癌作用的机制。方法在Bal b/c小鼠皮下注射C26细胞,建立皮下瘤模型,采用瘤内注射的方式,将实验分空白组(C)、lipo2000对照组(L)、紫杉醇组(T)、survivin反义核酸组(A)、survivin反义核酸联合紫杉醇组(A+T)5个不同组,观察肿瘤的生长状态,TUNEL法检测凋亡细胞,Western blot法检测survivin蛋白表达。结果 1各治疗组均达到了(T/C)<60%,与L组比较差异有统计学意义(P<0.05),体内证实给药干预有效;小鼠瘤重的抑瘤率结果显示,与C组比较,T、A、A+T各给药组均能抑制小鼠瘤重,差异具有统计学意义(P<0.05),从抑制肿瘤质量增长方面而言,二者联合用药[瘤重抑瘤率为(54.16±0.32)%]将紫杉醇[瘤重抑瘤率为(21.82±0.84)%]的抗癌活性提高了59%以上;2TUNEL法检测凋亡细胞:空白对照组几乎没有肿瘤细胞凋亡。T组及A组有一定量的凋亡细胞,以上试验结果提示,紫杉醇具有促进肿瘤细胞凋亡的能力,A+T不仅加强了对肿瘤细胞的杀伤作用,而且二者的协同作用可能对肿瘤耐药性有所影响,最终使得其促肿瘤细胞凋亡的作用尤为显著;3survivin蛋白表达:结果显示,A+T组survivin蛋白的表达明显降低,而不影响β-actin的表达,C组和L组相比无明显变化,T组、A组、A+T组A值的比值分别为0.895±0.011、0.704±0.121、0.345±0.019,经方差分析,A+T组与C、L、A、T组的表达量差异具有统计学意义(P<0.05)。结论 survivin反义核酸与紫杉醇联合用药,可能通过下调survivin蛋白的表达从而促进肿瘤细胞凋亡,联合用药可降低机体耐药性,发挥协同作用。Objective To explore the therapeutic effects of combined application of survivin antisense nucleic acid and taxol in subcutaneous xenograft mouse model of Balb/c and to preliminarily investigate the mechanism of the anticancer effects.Methods The model of subcutaneous tumor was established by hypodermic injection of C26 cells into Bal b/c mice.The mice were then randomly divided into five groups through the internal tumor injection：the blank group （C）,lipo2000 group （L）,paclitaxel group （T）,survivin antisense nucleic acid group （A）,and survivin antisense nucleic acid combined with paclitaxel group （A＋T）.We observed tumor growth,determined cell apoptosis by TUNEL method,and detected the expression of survivin by Western blot.Results ① All treatment groups had T/C〈60%,which was significantly different from that of group L （P 〈0.05）;the intervention was proved effective in vivo .The tumor inhibition rate of mice tumor weight showed that there were significantly curative effects in groups T,A and A＋ T compared with that in group C （P 〈 0.05 ）.The antitumor activity of paclitaxel （tumor inhibition rate of 21.82%±0.84%）could be improved by more than 59% through combination therapy （tumor inhibition rate of 54.1 6% ± 0.32%）concerning inhibition of tumor weight growth.② TUNEL method detected apoptotic cells：The tumor cells hardly had apoptosis in the blank group while T group and A group had a certain number of apoptotic cells.The experiment results suggested that PTX could promote tumor cell apoptosis,and that not only A＋T strengthened the effect in killing tumor cells,but also the synergy of both could influence tumor resistance and ultimately make the effect in promoting tumor cell apoptosis conspicuous.③ The expression of survivin protein：The results showed that the expression of survivin protein in group A ＋ T was obviously decreased without the expression of β-actin affected;it did not change significantly in group C compared with group L.The ratio of

关 键 词：皮下荷瘤 SURVIVIN 反义核酸 紫杉醇 联合用药 细胞凋亡 

分 类 号：R965.1[医药卫生—药理学]